Thecolonicepitheliumturnsoverrapidlyinhealth,thuslimitingtheaccumulationofgeneticdamage.However,thisrapidturnover,aswellasfrequent/prolongedexposuretobacteriallysynthesizedorenvironmentaltoxins,orboth,makesthelargeintestineespeciallyvulnerabletomalignancy.ColoncancerissecondinprevalenceonlytolungcancerinmenintheUnitedStatesandthirdbehindlungandbreastcancerinwomen.Withthedecreasedincidenceofcigarettesmokingandthereforelungcancer,coloncancermayassumeevengreatersignificance.Coloncancerariseswhennormalgeneticcontrolsontherateofepithelialproliferationaresubverted;initiallythisleadstogrowthofapolypandeventually,ifnotremoved,toaninvasivetumorthatmaymetastasizetootherpartsofthebody.Coloncancercanbesubdividedaccordingtothebasicnatureoftheunderlyingmoleculardefect,whichcanincludeoverexpressionofgrowthstimulatoryfactorsoramutationthatpreventsthecellsfromrespondingtofactorsthatwouldnormallybegrowthsuppressive.However,coloncancermortalitycanbereducedverysubstantiallybyearlydetectionandremovalofpolypswithmalignantpotential.Thishasdrivencurrentguidelinesforincreasedscreeningofevenasymptomaticmiddle-agedindividualsforcolonicabnormalitiesviacolonoscopy(inwhichaflexiblefiberoptictubeisinsertedintothecolontoinspectitsinterior),screeningforthepresenceofso-calledoccult(orhidden)bloodinthestoolderivedfromableedingpolyportumor,ornoninvasiveimagingtechniquessuchascomputedtomographyscans.
colon is driven by three transport processes. The first is electroneutral NaCl absorption, which is mediated by the same mechanism that drives NaCl absorption in the intestine (see
Fig. 30.17 ). NaCl absorption is stimulated by various growth factors, such as epidermal growth factor, and is inhibited by hormones and neurotransmitters that increase levels of cyclic adenosine monophosphate (cAMP) in colonic surface epithelial cells.
•Fig. 31.4 Mechanismofshort-chainfattyacid(SCFA)uptakebycolonocytes.ATP,adenosinetriphosphate;SMCT1,sodium/monocarboxylatecotransporter1.3Na˜SMCT1 SCFA used by colonocyte for intracellular metabolism ATP
The second transport process that drives fluid absorption in the colon is absorption of short-chain fatty acids, including acetate, propionate, and butyrate. These molecules are absorbed from the lumen by surface (and perhaps crypt) epithelial cells in an Na+-dependent fashion by a family of symporters related to the Na+-glucose symporter in the small intestine, and known as sodium-monocarboxylate transporters (SMCTs). Uptake of short-chain fatty acids by SMCTs located in the apical plasma membrane is driven by the low intracellular [Na+] established by the basolateral Na+,K+-ATPase (
Fig. 31.4 ). These short-chain fatty acids are used for energy by colonocytes. In addition, butyrate regulates expression of specific genes in colonic epithelial cells and may suppress development of a malignant phenotype. Expression of SMCT1 (also identified as SLC5A8) is reduced in some colon cancers, thereby leading to a reduction in butyrate uptake, which may contribute to malignant transformation.
The third absorptive process of major significance in the colon is absorption of Na+ (